Discussion
In this prospective cohort study, we show that neither a history of PTD, nor several other aspects of pregnancy history, are strongly associated with clinical restenosis following PCI in parous women <65 years.
Restenosis is an adverse outcome of PCI characterised by an inflammatory response to vessel wall damage.15 Increased inflammatory markers, such as C reactive protein, are seen in patients who develop restenosis after PCI.16 The pregnancy history aspects examined in this study are associated with the development of future CAD, possibly due to inflammation and/or endothelial dysfunction.
PTD is a risk factor for future maternal CAD.4 As stated above, the association has been partly attributed to that PTD and the development of future CAD share common pathways.17–19 Up to a quarter of the association between PTD and future maternal CAD has been shown to be explained by placental disorders such as pre-eclampsia, another female-specific risk factor for future maternal CAD.20
Women with a history of SGA are also at an increased risk for future cardiovascular disease (CVD).21 Even though the pathophysiological background to this association is overall inadequately understood, it has been suggested that a delivery complicated by SGA is associated with endothelial dysfunction and thus future development of CVD. Endothelial dysfunction, and in turn placental dysfunction, is recognised as an underlying pathway for development of future maternal CVD in other pregnancy complications such as pre-eclampsia.22–24
Parity is associated with a non-linear increased risk of maternal CVD,3 25 and the increased risk in women with parity >4 could be explained by an association with subclinical atherosclerosis in these women.26 Pregnancy in itself can be seen as an atherogenic state with dyslipidaemia, insulin resistance and weight gain, and it has been hypothesised that a prolonged exposure time to this state is what leads to atherosclerosis and increased risk of CVD in these women.26 Alternatively, raising a larger family may increase CVD risk via adverse effects on diet, sleep, physical activity and other behaviours, as well as weight gain.
Studies have shown a possible inverse association between age at first delivery and future CVD.2 Although socioeconomic factors are highlighted as the most likely explanation, it has also been suggested that the physiological changes a pregnancy entails could affect an adolescent body differently compared with an adult body. It could also be explained by the fact that some studies show an association between low maternal age and adverse pregnancy outcomes that are known predictors of future CVD (eg, PTD and delivering an SGA infant).27 28
We have previously reported that PTD warrants consideration as a risk factor in the secondary prevention setting post-coronary artery stenting.5 Though we report no association between the exposures in this study and clinical restenosis, studies like this could still be clinically relevant. As restenosis is often associated with angina or acute coronary syndrome and patients with restenosis often undergo TLR,15 studies that contribute to a better understanding of groups with a higher risk of adverse outcomes post-PCI can in turn contribute to a better patient outcome. As we have previously mentioned, further studies are needed to investigate how existing strategies for secondary prevention in the post-PCI stetting can reduce the risk of adverse outcomes postcoronary artery stenting in women with a history of PTD.
Strengths and limitations
The main strength of this study is the comprehensive and national study sample based on data from richly-completed well-known registers.11 13 The extensive nature of both the Medical Birth Register and SCAAR allowed us to include pregnancy data collected over decades and to adjust for several known predictors of restenosis, both procedure related and patient related. Another strength is our use of multiple imputation to account for missing data. However, this study also had some limitations. While our sample covers over a decade of national data, incident restenosis events are relatively rare, and our results do not exclude small to moderate associations for all exposures. Furthermore, we only included women age <65 years. As previously described, age is a strong predictor of worse outcome after PCI29 and older women have much less complete delivery history available in the Medical Birth Registry, which started in 1973. Additionally, we excluded women with PCI before 2006 as not all procedure-related variables were routinely collected before 2006. Our results are dependent on a consistency in PCI-related treatment of the women studied (eg, drug treatment before, during and after PCI). We believe an inconsistency to be unlikely given that pregnancy history is not considered in any relevant guidelines of acute cardiac care and was therefore not likely considered in the care of the women included in this study. Furthermore, we observed no major difference in the restenosis estimates by pregnancy history after adjusting for several patient-related and procedure-related predictors. The generalisation of the results could possibly be affected by the ethnic homogeneity of the study sample. Lastly, it should be mentioned that pregnancy dating using ultrasound was not widely used in Sweden until the 1970s, and at the beginning of the Medical Birth Register not all pregnancies were dated using ultrasound.